Role of a viral long non-coding RNA in virus superinfection exclusion

病毒长非编码RNA在病毒重复感染排除中的作用

• 批准号: 2316587
• 负责人: Svetlana Folimonova
• 金额: $ 75万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2316587&HistoricalAwards=false
• 关键词: Role; viral; long; non; coding

Superinfection exclusion (SIE) has been observed for viruses that infect humans, animals, and plants. The phenomenon occurs when cells carrying a virus become protected from a secondary infection by the same or closely related virus. SIE influences the pathogenesis and evolution of viral populations and could have a profound impact on treating viral infections. Despite its significance, our understanding of SIE is far from being complete. The elucidation of the mechanisms underlying this phenomenon will provide a foundation for the development of novel approaches to mitigate viral diseases of humans, animals, and agricultural crops. This project aims to unravel the mechanism of SIE of citrus tristeza virus (CTV), the largest non-segmented RNA virus of plants. CTV represents a valuable model system due to numerous well-characterized virus strains as well as a possibility to study the SIE phenomenon at the whole organism level. The project builds on the observations indicating that SIE by CTV functions through a unique mechanism, which involves multiple virus-encoded factors. The investigators' preliminary data suggest that a viral long non-coding RNA could play a role in this phenomenon. The project will utilize advanced molecular biology, microscopy, biochemistry, and genetic tools to further our understanding of viral SIE, interactions between virus variants in a host, and, importantly, the roles of viral lncRNAs, which represent a largely understudied research area, in the SIE phenomenon and in virus-host interactions. From the educational standpoint, this project will provide an excellent opportunity for new students to get up-close research experience and for training rising scientists, including members of underrepresented groups. The research results will be broadly disseminated through publishing in the leading peer-reviewed journals and presentations at scientific meetings.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

对感染人类、动物和植物的病毒已观察到重复感染排斥（SIE）。当携带病毒的细胞免受相同或密切相关的病毒的二次感染时，就会发生这种现象。SIE影响病毒种群的发病机制和进化，并可能对病毒感染的治疗产生深远的影响。尽管它意义重大，但我们对它的理解还远远不够完整。阐明这一现象背后的机制将为开发新的方法来减轻人类、动物和农作物的病毒性疾病提供基础。本项目旨在揭示柑橘tristeza病毒（CTV）的SIE机制，柑橘tristeza病毒是植物中最大的非节段RNA病毒。CTV是一个有价值的模型系统，因为它有许多特征明确的病毒株，也有可能在整个生物体水平上研究SIE现象。该项目建立在观察结果的基础上，表明CTV的SIE通过一种独特的机制起作用，该机制涉及多种病毒编码因子。研究人员的初步数据表明，病毒长链非编码RNA可能在这种现象中起作用。该项目将利用先进的分子生物学，显微镜学，生物化学和遗传工具来进一步了解病毒SIE，宿主病毒变体之间的相互作用，以及重要的是，病毒lncrna在SIE现象和病毒-宿主相互作用中的作用，这是一个很大程度上未被研究的研究领域。从教育的角度来看，该项目将为新生提供一个获得近距离研究经验的绝佳机会，并为培养新兴科学家，包括代表性不足的群体的成员提供机会。研究结果将通过在主要的同行评议期刊上发表和在科学会议上发表来广泛传播。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。